DESCRIPTION The long term objective of this research is to learn how the target- derived neurotrophins transmit information through axons. In preliminary studies, my post-doctoral mentors, have shown that neurotrophin receptor proteins (Trks) play a pivotal role in retrograde signaling through rat sciatic nerve axons. The specific aim of my research is to determine how information is conveyed by Trks (or upon Trks) through the axon. As described in the study plan, I will be working on compartmental cultures (Campenot cultures) of dorsal root ganglion neurons. I will install molecular tags on the ligand binding domain of Trk receptor protein expressed at the nerve ending. I will install molecular tags on the ligand binding domain of Trk receptor protein exposed at the nerve ending. I will determine whether the tagged Trk protein moves through the axon at the same rate as the retrograde signal. To go beyond the descriptive level, I will construct adenovirus expression vectors containing dominant negative mutations of dynamin. I will use these expression vectors to define the role of vesicular transport in retrograde signaling. These studies have practical implications for treatment of human peripheral neuropathies (secondary to diabetes or toxins), neurodegenerative diseases including amyotrophic lateral sclerosis and Alzheimer's, and spinal cord injuries. All these disease processes involve the death of neurons that have long projects and whose survival is regulated by neurotrophins.